`
`
`
`
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`____________________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`____________________
`
`
`GLAXOSMITHKLINE CONSUMER HEALTHCARE HOLDINGS (US) LLC,
`Petitioner
`
`v.
`
`CIPLA LTD.,
`Patent Owner
`
`____________________
`
`Case No. IPR2020-00368
`U.S. Patent No. 8,163,723
`____________________
`
`DECLARATION OF ROBERT P. SCHLEIMER, PH.D.
`
`
`
`

`

`IPR2020-00368 (U.S. Patent No. 8,163,723)
`Declaration of Robert P. Schleimer, Ph.D.
`
`
`B.
`
`C.
`
`TABLE OF CONTENTS
`
`I.
`Qualifications and Experience ..................................................................... 1
`II. Materials Considered ................................................................................... 3
`III. Relevant Legal Standards ............................................................................11
`IV. Priority Date of the ’723 Patent and Level of Ordinary Skill ......................13
`V.
`Technical Background ................................................................................15
`A. Azelastine and Fluticasone Nasal Sprays Were FDA-Approved and
`Marketed Commercially ...................................................................15
`1.
`Allergic Rhinitis......................................................................16
`2.
`Antihistamines for Nasal Administration ................................19
`3.
`Corticosteroids for Nasal Administration ................................28
`Azelastine and Fluticasone Nasal Sprays Were Co-Administered for
`Allergic Rhinitis................................................................................31
`The Prior Art Disclosed Pharmaceutical Nasal Formulations
`Comprising Both Azelastine and Fluticasone ....................................33
`1.
`Cramer (Ex. 1011) ..................................................................33
`2.
`Segal (Ex. 1012) .....................................................................41
`VI. The Challenged Claims ...............................................................................47
`VII. The Challenged Claims Would Have Been Obvious Over PDR 1999 in view
`of Segal .......................................................................................................47
`A.
`Independent Claim 1 .........................................................................49
`1.
`The art teaches all the claim limitations ..................................49
`2.
`A POSA would have been motivated to combine the art .........51
`3.
`A POSA would have had a reasonable expectation of success 56
`Claim 2 (Depends from Claim 1) ......................................................58
`Claim 3 (Depends from Claim 1) ......................................................59
`Claim 4 (Depends from Claim 1) ......................................................60
`Claim 5 (Depends from Claim 1) ......................................................61
`Claim 6 (Depends from Claim 1) ......................................................61
`Claim 7 (Depends from Claim 1) ......................................................63
`
`B.
`C.
`D.
`E.
`F.
`G.
`
`
`
`i
`
`

`

`IPR2020-00368 (U.S. Patent No. 8,163,723)
`Declaration of Robert P. Schleimer, Ph.D.
`
`H.
`Claim 8 (Depends from Claim 1) ......................................................63
`Claim 9 (Depends from Claim 1) ......................................................65
`I.
`Claim 10 (Depends from Claim 1) ....................................................66
`J.
`Claim 11 (Depends from Claim 10) ..................................................68
`K.
`Claim 12 (Depends from Claim 1) ....................................................69
`L.
`M. Claim 13 (Depends from Claim 12) ..................................................71
`N.
`Claim 14 (Depends from Claim 12) ..................................................73
`O.
`Claim 15 (Depends from Claim 1) ....................................................75
`P.
`Claim 16 (Depends from Claim 15) ..................................................76
`Q.
`Claim 17 (Depends from Claim 1) ....................................................78
`R.
`Claim 18 (Depends from Claim 1) ....................................................79
`S.
`Claim 19 (Depends from Claim 18) ..................................................80
`T.
`Claim 20 (Depends from Claim 18) ..................................................81
`U.
`Claim 21 (Depends from Claim 18) ..................................................82
`V.
`Claim 22 (Depends from Claim 1) ....................................................83
`W. Claim 23 (Depends from Claim 1) ....................................................84
`X.
`Claim 24 (Depends from Claim 15) ..................................................85
`Y.
`Claim 25 (Depends from Claim 17) ..................................................86
`Z.
`Claim 26 (Depends from Claim 18) ..................................................87
`AA. Claim 27 (Depends from Claim 18) ..................................................88
`BB. Claim 28 (Depends from Claim 1) ....................................................89
`VIII. The Challenged Claims Would Have Been Obvious Over Cramer in View of
`PDR 1999 ...................................................................................................91
`A.
`Independent Claim 1 .........................................................................92
`1.
`The art teaches all the claim limitations ..................................93
`2.
`A POSA would have been motivated to combine the art .........95
`3.
`A POSA would have had a reasonable expectation of success 98
`Claim 2 (Depends from Claim 1) .................................................... 100
`Claim 3 (Depends from Claim 1) .................................................... 101
`Claim 4 (Depends from Claim 1) .................................................... 102
`
`B.
`C.
`D.
`
`
`
`ii
`
`

`

`IPR2020-00368 (U.S. Patent No. 8,163,723)
`Declaration of Robert P. Schleimer, Ph.D.
`
`E.
`Claim 5 (Depends from Claim 1) .................................................... 103
`Claim 6 (Depends from Claim 1) .................................................... 104
`F.
`Claim 7 (Depends from Claim 1) .................................................... 105
`G.
`Claim 8 (Depends from Claim 1) .................................................... 106
`H.
`Claim 9 (Depends from Claim 1) .................................................... 107
`I.
`Claim 10 (Depends from Claim 1) .................................................. 109
`J.
`Claim 11 (Depends from Claim 10) ................................................ 111
`K.
`Claim 12 (Depends from Claim 1) .................................................. 112
`L.
`M. Claim 13 (Depends from Claim 12) ................................................ 115
`N.
`Claim 14 (Depends from Claim 12) ................................................ 118
`O.
`Claim 15 (Depends from Claim 1) .................................................. 121
`P.
`Claim 16 (Depends from Claim 15) ................................................ 122
`Q.
`Claim 17 (Depends from Claim 1) .................................................. 123
`R.
`Claim 18 (Depends from Claim 1) .................................................. 124
`S.
`Claim 19 (Depends from Claim 18) ................................................ 126
`T.
`Claim 20 (Depends from Claim 18) ................................................ 126
`U.
`Claim 21 (Depends from Claim 18) ................................................ 128
`V.
`Claim 22 (Depends from Claim 1) .................................................. 129
`W. Claim 23 (Depends from Claim 1) .................................................. 130
`X.
`Claim 24 (Depends from Claim 15) ................................................ 131
`Y.
`Claim 25 (Depends from Claim 17) ................................................ 132
`Z.
`Claim 26 (Depends from Claim 18) ................................................ 133
`AA. Claim 27 (Depends from Claim 18) ................................................ 134
`BB. Claim 28 (Depends from Claim 1) .................................................. 135
`IX. No Objective Indicia Demonstrating Nonobviousness .............................. 136
`A. No Unexpected Results Over the Closest Prior Art ......................... 137
`1.
`The closest prior art is a pharmaceutical nasal formulation with
`both azelastine and fluticasone .............................................. 138
`Co-administration of an oral antihistamine with an intranasal
`corticosteroid is not the closest prior art ................................ 139
`
`2.
`
`
`
`iii
`
`

`

`IPR2020-00368 (U.S. Patent No. 8,163,723)
`Declaration of Robert P. Schleimer, Ph.D.
`
`
`3.
`
`4.
`
`5.
`
`6.
`
`2.
`
`3.
`
`4.
`
`2.
`
`The September 2010 Malhotra Declaration does not compare
`the claimed invention to the closest prior art ......................... 148
`The August 2011 Maus Declaration does not compare the
`claimed invention to the closest prior art ............................... 150
`Cipla did not compare the claimed invention to the closest prior
`art during the Apotex litigation ............................................. 157
`The November 2017 Carr Declaration does not compare the
`claimed invention to the closest prior art ............................... 158
`No Satisfaction of a Long-Felt But Unmet Need ............................. 160
`1.
`The August 2011 Rajan Declaration does not show that the
`claimed invention satisfied a long-felt need .......................... 160
`The August 2011 Chopra Declaration does not show that the
`claimed invention satisfied a long-felt need .......................... 162
`Cipla did not show that the claimed invention satisfied a long-
`felt need during the Apotex litigation .................................... 164
`The November 2017 Carr Declaration does not show that the
`claimed invention satisfied a long-felt need .......................... 164
`No Industry Praise .......................................................................... 166
`1.
`Leung does not constitute industry praise of the claimed
`invention ............................................................................... 166
`GlobalData does not constitute industry praise of the claimed
`invention ............................................................................... 167
`D. No Prior Art Teaching Away .......................................................... 168
`Operability of Cramer’s Example 3 .......................................................... 169
`X.
`XI. Conclusion ................................................................................................ 172
`
`
`B.
`
`C.
`
`
`
`iv
`
`

`

`IPR2020-00368 (U.S. Patent No. 8,163,723)
`Declaration of Robert P. Schleimer, Ph.D.
`
`
`I, Robert P. Schleimer, Ph.D., do hereby declare:
`
`1.
`
`I am making this Declaration at the request of GlaxoSmithKline
`
`Consumer Healthcare Holdings (US) LLC (“GSK”) in the matter of Inter Partes
`
`Review (“IPR”) of U.S. Patent No. 8,163,723 (“’723 Patent”). I understand that
`
`the ’723 Patent is owned by Cipla Ltd. (“Patent Owner”) and licensed to Mylan
`
`Pharmaceuticals, which acquired Meda Pharmaceuticals.
`
`2.
`
`I am being compensated for my work on this matter at my standard
`
`consulting rate, which is $750 per hour for time spent providing testimony, with a
`
`four-hour minimum per day of testimony, and $500 per hour for time spent on
`
`other tasks, such as analyzing documents and drafting declarations. My
`
`compensation in no way depends on the outcome of this proceeding or the content
`
`of my testimony, and my opinions are based on my own views of the patented
`
`technology and the prior art.
`
`I.
`
`QUALIFICATIONS AND EXPERIENCE
`3. My area of expertise is in the field of allergy and immunology. At
`
`Northwestern University’s Feinberg School of Medicine, I am presently the Chief
`
`of the Division of Allergy and Immunology in the Department of Medicine, the
`
`Roy and Elaine Patterson Professor of Medicine, and a Professor of Medicine in
`
`the Division of Allergy and Immunology. I am also a Professor in the Departments
`
`of Microbiology-Immunology and Otolaryngology - Head and Neck Surgery. My
`
`- 1 -
`
`

`

`research areas include the mechanisms of pathogenesis and treatment of a variety
`
`IPR2020-00368 (U.S. Patent No. 8,163,723)
`Declaration of Robert P. Schleimer, Ph.D.
`
`
`of allergic and inflammatory diseases associated with allergy, including chronic
`
`rhinosinusitis, asthma, hay fever, rhinitis, food allergy and others. I also study the
`
`mechanisms of action of anti-inflammatory glucocorticoids, with a focus on the
`
`molecular and cellular mechanisms underlying disease and steroid action as well as
`
`developing strategies for new treatments.
`
`4.
`
`I obtained a Bachelor of Arts in Biology from the University of
`
`California, San Diego in 1974 and a Ph.D. from the University of California, Davis
`
`in Pharmacology, Toxicology, and Immunology in 1979.
`
`5.
`
`Additionally, I am a named author on over 375 scientific papers, have
`
`served as an editor or on the editorial board of ten different journals, and have
`
`trained a large number of graduate and undergraduate students as well as
`
`postdoctoral fellows.
`
`6.
`
`I have previously provided expert opinions about the ’723 Patent and
`
`related U.S. Patent Nos. 8,168,620 (“’620 Patent”) and 9,259,428 (“’428 Patent”)
`
`in a patent infringement litigation. I have also previously provided expert opinions
`
`about the ’620 Patent in a prior IPR proceeding at the U.S. Patent and Trademark
`
`Office (“USPTO”). I understand that these matters are captioned and were
`
`resolved as follows: (1) Meda Pharmaceuticals, Inc. v. Apotex Inc., No. 14-cv-
`
`01453 (D. Del.) (dismissed by stipulation on May 18, 2017) (“the Apotex
`
`- 2 -
`
`

`

`litigation”); and (2) Argentum Pharmaceuticals LLC v. Cipla Ltd., IPR2017-00807
`
`IPR2020-00368 (U.S. Patent No. 8,163,723)
`Declaration of Robert P. Schleimer, Ph.D.
`
`
`(PTAB) (terminated by joint motion on May 21, 2018) (“the Argentum IPR”).
`
`7. My curriculum vitae is provided as Appendix A to this Declaration.
`
`8.
`
`In view of my experiences and expertise outlined above and provided
`
`in my curriculum vitae, I am an expert in the field of allergy and immunology.
`
`II. MATERIALS CONSIDERED
`I have considered the following documents in preparing this
`9.
`
`Declaration:
`
`Exhibit
`No.
`Ex. 1001
`Ex. 1002
`
`Exhibit Name
`’620 Patent
`’723 Patent
`
`Ex. 1003
`
`’428 Patent
`
`Ex. 1004
`
`’585 Patent
`
`Ex. 1005
`
`’620 File History
`
`Exhibit
`U.S. Patent No. 8,168,620 (issued May 1, 2012)
`U.S. Patent No. 8,163,723 (issued April 24,
`2012)
`U.S. Patent No. 9,259,428 (issued Feb. 16,
`2016)
`U.S. Patent No. 9,901,585 (issued Feb. 27,
`2018)
`Excerpts from the prosecution file wrapper of
`the ’620 Patent:
`(A) Amendments and Response to Office
`Action Dated January 23, 2009 (July 23,
`2009) (“July 2009 ’620 Amendment”)
`(pages 1-20);
`(B) Declaration under 37 C.F.R. § 1.132 by
`Geena Malhotra (July 3, 2009) (“July 2009
`Malhotra Declaration”), with Exhibits A-C
`(pages 21-44);
`(C) Final Office Action (April 28, 2010)
`(“April 2010 ’620 Final Office Action”)
`(pages 45-65);
`
`- 3 -
`
`

`

`Exhibit
`No.
`
`Exhibit Name
`
`IPR2020-00368 (U.S. Patent No. 8,163,723)
`Declaration of Robert P. Schleimer, Ph.D.
`
`
`Exhibit
`(D) Amendments and Response to Final Office
`Action Dated April 28, 2010 (Sept. 24,
`2010) (“September 2010 ’620 Amendment”)
`(pages 66-87);
`(E) Declaration under 37 C.F.R. § 1.132 by
`Geena Malhotra (Sept. 23, 2010)
`(“September 2010 Malhotra Declaration”),
`with Exhibits A-D (pages 88-117);
`(F) Office Action (Feb. 16, 2011)
`(“February 2011 ’620 Office Action”)
`(pages 118-134);
`(G) Amendments and Response to Office
`Action Dated February 16, 2011 (Aug. 16,
`2011) (“August 2011 ’620 Amendment”)
`(pages 135-164);
`(H) Declaration under 37 C.F.R. § 1.132 by
`Nikhil Chopra (Dec. 8, 2011)
`(“December 2011 Chopra Declaration”),
`with Exhibit A (pages 165-173);
`(I) Declaration under 37 C.F.R. § 1.132 by
`Geena Malhotra (Aug. 12, 2011)
`(“August 2011 Malhotra Declaration”),
`with Exhibits A-C (pages 174-196);
`(J) Declaration under 37 C.F.R. § 1.132 by
`Joachim Maus (Aug. 16, 2011)
`(“August 2011 Maus Declaration”), with
`Exhibits A-H (pages 197-297);
`(K) Declaration under 37 C.F.R. § 1.132 by
`Sujeet Rajan (Aug. 16, 2011) (“August 2011
`Rajan Declaration”), with Exhibit A
`(pages 298-318);
`(L) Notice of Allowance and Fees Due (Oct. 3,
`2011) with Notice of Allowability
`(“’620 Notice of Allowance”) (pages 319-
`327)
`(M) Notice of Allowance and Fees Due
`(Jan. 30, 2012) with Supplemental Notice of
`
`- 4 -
`
`

`

`Exhibit
`No.
`
`Exhibit Name
`
`Ex. 1006
`
`’723 File History
`
`Ex. 1007
`
`’428 File History
`
`Ex. 1008
`
`’585 File History
`
`IPR2020-00368 (U.S. Patent No. 8,163,723)
`Declaration of Robert P. Schleimer, Ph.D.
`
`
`Exhibit
`Allowability (“’620 Supplemental Notice of
`Allowance”) (pages 328-342)
`Excerpts from the prosecution file wrapper of
`the ’723 Patent:
`(A) Interview Summary (Nov. 23, 2011)
`(“November 2011 ’723 Interview
`Summary”) (pages 1-3);
`(B) Preliminary Amendment (Dec. 12, 2011)
`(“December 2011 ’723 Preliminary
`Amendment”) (pages 4-14);
`(C) Notice of Allowance and Fees Due (Jan. 26,
`2012) (“’723 Notice of Allowance”)
`(pages 15-23)
`Excerpts from the prosecution file wrapper of
`the ’428 Patent:
`(A) Office Action (May 7, 2015) (“May 2015
`’428 Office Action”) (pages 1-8);
`(B) Interview Summary (May 7, 2015)
`(“May 2015 ’428 Interview Summary”)
`(pages 9-10);
`(C) Amendments and Response to Office
`Action Dated May 7, 2015 (Aug. 7, 2015)
`(“August 2015 ’428 Amendment”)
`(pages 11-22);
`(D) Supplemental Response to Office Action
`Dated May 7, 2015 (Oct. 14, 2015)
`(“October 2015 ’428 Supplemental
`Response”) (pages 23-32);
`(E) Notice of Allowance and Fees Due
`(Nov. 18, 2015) (“’428 Notice of
`Allowance”) (pages 33-41)
`Excerpts from the prosecution file wrapper of
`the ’585 Patent:
`(A) Office Action (Feb. 1, 2017)
`(“February 2017 ’585 Office Action”)
`(pages 1-9);
`
`- 5 -
`
`

`

`Exhibit
`No.
`
`Exhibit Name
`
`Ex. 1009
`
`Phillipps
`
`Ex. 1010
`
`PDR 1999
`
`Ex. 1011
`
`Ex. 1012
`
`Ex. 1013
`
`Cramer
`
`Segal
`
`Hettche
`
`Ex. 1014
`
`PDR 2000
`
`Ex. 1017
`
`Stellato
`
`Ex. 1018
`
`Johnson
`
`Ex. 1019
`
`Dykewicz
`
`Ex. 1020
`
`Falser
`
`IPR2020-00368 (U.S. Patent No. 8,163,723)
`Declaration of Robert P. Schleimer, Ph.D.
`
`
`Exhibit
`(B) Response to Office Action Dated
`February 1, 2017 (Aug. 1, 2017)
`(“August 2017 ’585 Response”) (pages 10-
`29);
`(C) Notice of Allowance and Fees Due (Oct. 31,
`2017) (“’585 Notice of Allowance”)
`(pages 30-42)
`U.S. Patent No. 4,335,121 (issued June 15,
`1982)
`“Flonase” and “Astelin,” in the Physicians’
`Desk Reference (1999) at 1122-1124 and 3191-
`3192
`European Patent Application Publication No.
`EP 0,780,127 A1 (published June 25, 1997)
`International Patent Application Publication No.
`WO 98/48839 (published November 5, 1998)
`U.S. Patent No. 5,164,194 (issued Nov. 17,
`1992)
`“Flonase” and “Astelin,” in the Physicians’
`Desk Reference (2000) at 1184-1186 and 3147-
`3148
`Stellato, et al., “An In Vitro Comparison of
`Commonly Used Topical Glucocorticoid
`Preparations,” Journal of Allergy and Clinical
`Immunology 104(3):623-629 (1999)
`Johnson, “Development of Fluticasone
`Propionate and Comparison with Other Inhaled
`Corticosteroids,” Journal of Allergy and
`Clinical Immunology, 101(4):S434-S439 (1998)
`Dykewicz, et al., “Diagnosis and Management
`of Rhinitis: Complete Guidelines of the Joint
`Task Force on Practice Parameters in Allergy,
`Asthma and Immunology,” Annals of Allergy,
`Asthma & Immunology 81(5):478-518 (1998)
`Falser, et al., “Comparative Efficacy and Safety
`of Azelastine and Levocabastine Nasal Sprays
`
`- 6 -
`
`

`

`Exhibit
`No.
`
`Exhibit Name
`
`Ex. 1021
`
`Berger
`
`Ex. 1022
`
`Cauwenberge
`
`Ex. 1023
`
`Spector
`
`Ex. 1024
`
`Bousquet
`
`Ex. 1025
`
`Kusters
`
`Ex. 1026
`
`Wihl
`
`Ex. 1027
`
`Lieberman
`
`Ex. 1028
`
`Harris
`
`IPR2020-00368 (U.S. Patent No. 8,163,723)
`Declaration of Robert P. Schleimer, Ph.D.
`
`
`Exhibit
`in Patients with Seasonal Allergic Rhinitis,”
`Arzneimittel Forschung 51(5):387-393 (2001)
`Berger, et al., “Double-Blind Trials of
`Azelastine Nasal Spray Monotherapy Versus
`Combination Therapy with Loratadine Tablets
`and Beclomethasone Nasal Spray in Patients
`with Seasonal Allergic Rhinitis,” Annals of
`Allergy, Asthma & Immunology 82(6):535-
`541(1999)
`Cauwenberge, et al., “Consensus Statement on
`the Treatment of Allergic Rhinitis,” Allergy
`55(2):116-134 (2000)
`Spector, “Ideal Pharmacology for Allergic
`Rhinitis,” Journal of Allergy and Clinical
`Immunology 103(3):S386-S387 (1999)
`Bousquet, et al., “Management of Allergic
`Rhinitis and Its Impact on Asthma,” Journal of
`Allergy and Clinical Immunology 108(5):S147-
`S334 (2001)
`Kusters, et al., “Effects of Antihistamines on
`Leukotriene and Cytokine Release from
`Dispersed Nasal Polyp Cells,” Arzneimittel
`Forschung 52(2):97-102 (2002)
`Wihl, et al., “Effect of the Nonsedative H1-
`Receptor Antagonist Astemizole in Perennial
`Allergic and Nonallergic Rhinitis,” Journal of
`Allergy and Clinical Immunology 75(6):720-
`727 (1985)
`Lieberman, “Treatment Update: Nonallergic
`Rhinitis,” Allergy and Asthma Proceedings
`22(4):199-202 (2001)
`Harris, et al., “Intranasal Administration of
`Peptides: Nasal Deposition, Biological
`Response, and Absorption of Desmopressin,”
`Journal of Pharmaceutical Sciences
`75(11):1085-1088 (1986)
`
`- 7 -
`
`

`

`Exhibit
`No.
`
`Exhibit Name
`
`Ex. 1029
`
`Nielsen 2003
`
`Ex. 1030
`
`Watts
`
`Ex. 1031
`
`Juniper 1997
`
`Ex. 1034
`
`Ratner 1998
`
`Ex. 1035
`
`Drouin
`
`Ex. 1036
`
`Simpson
`
`Ex. 1037
`
`Howarth
`
`Ex. 1038
`
`Brooks
`
`IPR2020-00368 (U.S. Patent No. 8,163,723)
`Declaration of Robert P. Schleimer, Ph.D.
`
`
`Exhibit
`Nielsen & Dahl, “Comparison of Intranasal
`Corticosteroids and Antihistamines in Allergic
`Rhinitis, A Review of Randomized, Controlled
`Trials,” American Journal of Respiratory
`Medicine 2(1):55-65 (2003)
`Watts, et al., “Modulation of Allergic
`Inflammation in the Nasal Mucosa of Allergic
`Rhinitis Sufferers with Topical Pharmaceutical
`Agents,” Frontiers in Pharmacology 10(294):1-
`22 (2019)
`Juniper, “First-line Treatment of Seasonal
`(Ragweed) Rhinoconjunctivitis),” Canadian
`Medical Association Journal 156(8):1123-1131
`(1997)
`Ratner et al., “A Comparison of the Efficacy of
`Fluticasone Propionate Aqueous Nasal Spray
`and Loratadine, Alone and in Combination, for
`the Treatment of Seasonal Allergic Rhinitis,”
`The Journal of Family Practice 47(1):118-125
`(1998)
`Drouin, et al. “Adding Loratadine to Topical
`Nasal Steroid Therapy Improves Moderately
`Severe Seasonal Allergic Rhinoconjunctivitis,”
`Advances in Therapy 12(6):340-349 (1995)
`Simpson, “Budesonide and Terfenadine,
`Separately and in Combination, in the
`Treatment of Hay Fever,” Annals of Allergy
`73(6):497-502 (1994)
`Howarth, “A Comparison of the Anti-
`Inflammatory Properties of Intranasal
`Corticosteroids and Antihistamines in Allergic
`Rhinitis,” Allergy 62:6-11 (2000)
`Brooks, et al., “Spectrum of Seasonal Allergic
`Rhinitis Symptom Relief with Topical Corticoid
`and Oral Antihistamine Given Singly or in
`Combination,” American Journal of Rhinology
`10(3):193-199 (1996)
`
`- 8 -
`
`

`

`Exhibit
`No.
`
`Exhibit Name
`
`Ex. 1039
`
`Juniper 1989
`
`Ex. 1040
`
`Benincasa
`
`Ex. 1041
`
`Galant
`
`Ex. 1042
`
`Nielsen 2001
`
`Ex. 1043
`
`November 2017
`Carr Declaration
`
`Ex. 1044
`
`Nelson
`
`Ex. 1045
`
`Ratner 2008
`
`Ex. 1046 Cipla Response in
`Argentum IPR
`Pipkorn
`
`Ex. 1047
`
`IPR2020-00368 (U.S. Patent No. 8,163,723)
`Declaration of Robert P. Schleimer, Ph.D.
`
`
`Exhibit
`Juniper et al., “Comparison of Beclomethasone
`Dipropionate Aqueous Nasal Spray,
`Astemizole, and the Combination in the
`Prophylactic Treatment of Ragweed Pollen-
`Induced Rhinoconjunctivitis,” Journal of
`Allergy and Clinical Immunology 83(3):627-
`633 (1989)
`Benincasa & Lloyd, “Evaluation of Fluticasone
`Propionate Aqueous Nasal Spray Taken Alone
`and in Combination with Cetirizine in the
`Prophylactic Treatment of Seasonal Allergic
`Rhinitis,” Drug Investigation, 8(4): 225-233
`(1994)
`Galant & Wilkinson, “Clinical Prescribing of
`Allergic Rhinitis Medication in the Preschool
`and Young School-Age Child,” Biodrugs
`15(7):453-463 (2001)
`Nielsen et al., “Intranasal Corticosteroids for
`Allergic Rhinitis,” Drugs 61(11):1563-1579
`(2001)
`Second Declaration of Warner Carr, M.D.,
`IPR2017-00807 (Ex. 2147) (Nov. 20, 2017)
`Nelson, “Mechanisms of Intranasal Steroids in
`the Management of Upper Respiratory Allergic
`Diseases,” Journal of Allergy and Clinical
`Immunology 104(4):S138-S143 (1999)
`Ratner et al., “Combination Therapy with
`Azelastine Hydrochloride Nasal Spray and
`Fluticasone Propionate Nasal Spray in the
`Treatment of Patients with Seasonal Allergic
`Rhinitis,” Annals of Allergy, Asthma &
`Immunology 100:74-81 (2008)
`Patent Owner Response, IPR2017-00807
`(Paper 21) (Nov. 20, 2017)
`Pipkorn et al., “Inhibition of Mediator Release
`in Allergic Rhinitis by Pretreatment with
`
`- 9 -
`
`

`

`Exhibit
`No.
`
`Exhibit Name
`
`Ex. 1048
`
`Salib
`
`Ex. 1049
`
`Backhouse
`
`Ex. 1050
`
`Ratner 1994
`
`Ex. 1051
`
`Cipla’s Post-Trial
`Sur-Reply Brief in
`Apotex Litigation
`
`Ex. 1052
`
`Leung
`
`Ex. 1053
`
`GlobalData
`
`Ex. 1054
`
`Ex. 1055
`
`Ex. 1056
`
`Cipla Preliminary
`Response in
`Argentum IPR
`Institution
`Decision in
`Argentum IPR
`Flonase Ad
`
`
`
`
`IPR2020-00368 (U.S. Patent No. 8,163,723)
`Declaration of Robert P. Schleimer, Ph.D.
`
`
`Exhibit
`Topical Glucocorticosteroids,” New England
`Journal of Medicine 316(24):1506-1510 (1987)
`Salib & Howarth, “Safety and Tolerability
`Profiles of Intranasal Antihistamines and
`Intranasal Corticosteroids in the Treatment of
`Allergic Rhinitis,” Drug Safety 26(12):863-893
`(2003)
`Backhouse et al., “Treatment of Seasonal
`Allergic Rhinitis with Flunisolide and
`Terfenadine,” Journal of International Medical
`Research 14(1):35-41 (1986)
`Ratner et al., “A Double-Blind, Controlled Trial
`to Assess the Safety and Efficacy of Azelastine
`Nasal Spray in Seasonal Allergic Rhinitis,”
`Journal of Allergy and Clinical Immunology
`94(5):818-825 (1994)
`Plaintiffs’ Post-Trial Sur-Reply Brief on
`Objective Indicia of Nonobviousness, Meda
`Pharmaceuticals Inc. v. Apotex Inc., No. 1:14-
`cv-01453-LPS (D.I. 163) (D. Del.)
`Leung, et al. “The Editors’ Choice: MP29-02:
`A Major Achievement in the Treatment of
`Allergic Rhinitis,” Journal of Allergy and
`Clinical Immunology 129(5):1216-1217 (2012)
`GlobalData, “Allergic Rhinitis - Global Drug
`Forecast and Market Analysis to 2024,” 1-281
`(Sept. 2015)
`Patent Owner Preliminary Response, IPR2017-
`00807 (Paper 7) (May 30, 2017)
`
`Institution Decision, IPR2017-00807 (Paper 19)
`(Oct. 30, 2017)
`“Flonase,” in Special Advertising Section of
`Sports Illustrated 93(11) (Sept. 18, 2000)
`
`- 10 -
`
`

`

`IPR2020-00368 (U.S. Patent No. 8,163,723)
`Declaration of Robert P. Schleimer, Ph.D.
`
`
`III. RELEVANT LEGAL STANDARDS
`10. The opinions I express in this Declaration involve the application of
`
`my technical knowledge and experience to the evaluation of certain prior art with
`
`respect to the ’723 Patent. In addition, I understand that the following legal
`
`principles apply.
`
`11.
`
`I understand that patent claims may be independent or dependent; that
`
`an independent claim includes only the limitations it recites; and that a dependent
`
`claim includes the limitations it recites, as well as the limitations recited in the
`
`claim or claims from which it depends.
`
`12.
`
`I understand that claims are given their ordinary meaning to a person
`
`having ordinary skill in the art (“POSA”) at the relevant timeframe in light of the
`
`claim language, patent specification, and prosecution history.
`
`13.
`
`I understand that a patent claim is unpatentable for obviousness if the
`
`invention described in the claim would have been obvious to a POSA at the time
`
`the invention was made, taking into account (1) the scope and content of the prior
`
`art, (2) the differences between the prior art and the claimed invention, (3) the level
`
`of ordinary skill in the art, and (4) any objective indicia of nonobviousness,
`
`including unexpected results over the closest prior art, satisfaction by the claimed
`
`invention of a long-felt but previously unmet need, industry praise, and prior art
`
`teaching away from the claimed invention.
`
`- 11 -
`
`

`

`IPR2020-00368 (U.S. Patent No. 8,163,723)
`Declaration of Robert P. Schleimer, Ph.D.
`
`
`I understand that there are multiple rationales that can be used to
`
`14.
`
`support a conclusion of obviousness. I understand, for example, that a patent claim
`
`is unpatentable for obviousness if (1) all the claim limitations are taught in the
`
`prior art, (2) a POSA would have been motivated to combine or modify the prior
`
`art to arrive at the claimed invention, and (3) a POSA would have had a reasonable
`
`expectation of success in combining or modifying the prior art to arrive at the
`
`claimed invention. I understand that the motivation to combine or modify the prior
`
`art may be found in the prior art or in the knowledge generally available to a POSA
`
`as of the priority date.
`
`15.
`
`I understand that nonobviousness of a claimed invention may be
`
`supported by certain objective indicia of nonobviousness. I understand that the
`
`Patent Owner has the burden to (1) present any alleged objective indicia of
`
`nonobviousness, such as unexpected results over the closest prior art, satisfaction
`
`by the claimed invention of a long-felt but previously unmet need, industry praise,
`
`and prior art teaching away from the claimed invention; and (2) demonstrate that
`
`such evidence supports nonobviousness of the claimed invention.
`
`- 12 -
`
`

`

`IPR2020-00368 (U.S. Patent No. 8,163,723)
`Declaration of Robert P. Schleimer, Ph.D.
`
`
`IV. PRIORITY DATE OF THE ’723 PATENT AND LEVEL OF
`ORDINARY SKILL
`I understand that I must consider the claims of the ’723 Patent and the
`16.
`
`prior art from the perspective of a POSA as of the priority date. I understand that a
`
`POSA would be aware of all the pertinent art at that time.
`
`17. According to the face of the ’723 Patent, it is related to U.S. Patent
`
`Application No. 10/518,016 (“the ’620 Patent application”), which is the national
`
`stage application of International Patent Application No. PCT/GB03/02557, filed
`
`on June 13, 2003. (’723 Patent, (60).) According to the face of the ’723 Patent,
`
`the International Patent Application claims priority to Great Britain Patent
`
`Application No. GB 0213739.6, filed on June 14, 2002. (Id., (30); see also id.,
`
`1:4-15.)
`
`18.
`
`I understand that the prior art discussed in this Declaration is prior art
`
`regardless of whether or not the ’723 Patent is entitled to claim priority to the
`
`June 14, 2002, date. I take no position in this Declaration on whether the
`
`’723 Patent is entitled to claim priority to that date. I nonetheless refer to June 14,
`
`2002, as “the priority date.”
`
`19. Even though I am an expert, I am qualified to render opinions as to
`
`the level of ordinary skill in the art at the relevant times.
`
`- 13 -
`
`

`

`IPR2020-00368 (U.S. Patent No. 8,163,723)
`Declaration of Robert P. Schleimer, Ph.D.
`
`
`I understand that several factors are considered in determining the
`
`20.
`
`level of ordinary skill in the art. These factors include (1) the types of problems
`
`encountered in the art, (2) the prior art solutions to those problems, (3) the rapidity
`
`with which innovations are made, (4) the sophistication of the technology, and
`
`(5) the educational level of active workers in the field.
`
`21. Based on these factors as well as my experience and expertise, a
`
`POSA in the field of pharmaceutical formulations for allergy/immunology as of the
`
`priority date would have been part of a multidisciplinary team including a
`
`clinician/scientist and formulator.
`
`22. The clinician/scientist in this field would have had an M.D., a Pharm.
`
`D., or a Ph.D. in the field of allergy/immunology and/or pharmacology (or the
`
`equivalent), and at least three years of experience in treating or researching the
`
`treatment of allergic rhinitis, including with nasally administered steroids and
`
`antihistamines. A higher level of education or specific skill might make up for less
`
`experience, and vice-versa.
`
`23.
`
`I understand that another consultant for GSK will opine on the level of
`
`skill for the formulator.
`
`24. This level of skill applies to all of my obviousness analyses and
`
`opinions in this Declaration. I reserve the right to supplement